Back to Search
Start Over
Hyperglycemia Induces Inflammatory Response of Human Macrophages to CD163-Mediated Scavenging of Hemoglobin-Haptoglobin Complexes
- Source :
- International Journal of Molecular Sciences, Vol 23, Iss 1385, p 1385 (2022), International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1385
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications.
- Subjects :
- QH301-705.5
Antigens, Differentiation, Myelomonocytic
Receptors, Cell Surface
Hemolysis
Monocytes
Catalysis
scavenger receptor
Inorganic Chemistry
Hemoglobins
Antigens, CD
Humans
Biology (General)
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Cells, Cultured
Spectroscopy
Receptors, Scavenger
Haptoglobins
Organic Chemistry
General Medicine
Endocytosis
macrophages
Computer Science Applications
Chemistry
inflammation
diabetes mellitus
CD163
hyperglycemia
hemoglobin-haptoglobin complexes
Diabetic Angiopathies
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....bb5fc871cf8a6b09c76b1c6664c5c810
- Full Text :
- https://doi.org/10.3390/ijms23031385